Diagnostic methods for assessing the condition of arteriosclerosis, which have already been put to practical use, include, for example, the four methods described below.
“Ankle-brachial pressure index”: When blood pressure is measured at the arm and ankle levels in the supine position, the ankle blood pressure is normally slightly higher. However, the narrowing of a blood vessel reduces the downstream blood pressure, which results in a decrease in the ratio of ankle blood pressure to brachial blood pressure (ABI). A decrease in ABI not only indicates arteriosclerosis in the artery of the lower limb but also suggests systemic arteriosclerosis.
“Pulse wave velocity test”: A method for estimating the progression of arteriosclerosis by assessing arterial stiffness. In healthy individuals, blood vessels are elastic and thus vascular walls absorb vibration, resulting in a reduction in pulse wave velocity. As arteriosclerosis advances, the wave velocity increases. Thus, the progression of arteriosclerosis can be estimated using the velocity as an indicator.
“Carotid ultrasound examination”: A method for estimating the progression of systemic arteriosclerosis by observing carotid arteries which run very close to the surface of skin and have an interior condition that is easy to observe by ultrasound.
“MR angiography (MRA)” and “CT angiography (CTA)”: Angiography was used as a major diagnostic imaging method for vascular diseases, but image information that is almost comparable to angiography but obtained in a less invasive manner has become available. The advantages of CTA include: (1) high spatial resolution; (2) simple examination; and (3) superiority in detecting calcified lesions.
The above-described “ankle-brachial pressure index” and “pulse wave velocity test” can neither identify the site of atherosclerosis nor diagnose the progression at each site. Thus, these methods only provide indirect scores to assess arteriosclerosis.
Unlike pulse wave velocity test or such, “carotid ultrasound examination” is superior in that it enables direct graphical observation of the inside of blood vessels. However, the condition of vascular wall is assessed based on the contrasting density and shape in ultrasonic images, and thus clinicians and laboratory technicians who conduct the test are required to have skills. Furthermore, the test cannot identify the site of atherosclerosis or diagnose the progression at individual sites in blood vessels other than the carotid artery.
Meanwhile, methods for monitoring the progression of arteriosclerosis include ELISA systems for measuring the oxidized LDL/β2GPI complex in blood (Japanese Patent Nos. 3370334 and 3898680; WO2003/022866, WO2004/023141). However, conventional ELISA for measuring the oxidized LDL/β2GPI complex can be used to estimate the size but not the site of atherosclerotic plaque.
Meanwhile, even when MRI or radiolabeled imaging is used, the condition of vascular wall is assessed based on the contrasting densities and shapes in ultrasonic images, and thus clinicians and laboratory technicians who conduct the test are required to have skills and expertise (U.S. Pat. Nos. 6,716,410 and 6,375,925).
Prior art documents related to the present invention include:    [Patent Document 1] Japanese Patent No. 3370334    [Patent Document 2] Japanese Patent No. 3898680    [Patent Document 3] WO 2003/022866    [Patent Document 4] WO 2004/023141    [Patent Document 5] Japanese Patent Application Kohyo Publication No. (JP-A) 2001-506983 (unexamined Japanese national phase publication corresponding to a non-Japanese international publication)    [Patent Document 6] Japanese Patent No. 4044972    [Patent Document 7] U.S. Pat. No. 6,716,410    [Patent Document 8] U.S. Pat. No. 6,375,925    [Non-patent Document 1] Journal of Biological Chemistry 269, 15274-15279, 1994